Phase II Trial of Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Clinical Response
研究概览
简要总结
Background:
Medullary thyroid cancer (MTC) is a tumor of the thyroid gland. Surgery is the only current treatment to cure it. The drug pembrolizumab (MK-3475) is a new type of cancer therapy. It works by allowing the immune system to detect and kill tumor cells.
Objective:
To test how pembrolizumab affects people with MTC and if it can offer them clinical benefit.
Eligibility:
People ages 18 and older with MTC
Patients who have recurrent or metastatic MTC, for whom surgery is not a curative option
Patients with some imaging evidence of MTC
Patients with minimal symptoms related to MTC
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, and heart tests
- Computed tomography (CT) scan or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body.
- Bone scan
Participants will be put in a group based on their treatment history:
- Group 1 if they have had an immune stimulating cancer vaccine
- Group 2 if they have had no vaccine
Participants will receive the study drug as a 30-minute intravenous (IV) infusion every 3 weeks. Treatment will continue for up to 2 years as long as they tolerate it and their disease does not get worse.
Participants will have physical exams and blood tests on the day of each infusion. They will have CT and bone scans every 3 months.
Participants may save biopsies before treatment and after starting treatment.
Participants will have a final visit 3-4 weeks after stopping treatment. This will include a physical exam and blood and heart tests.
After this study, participants can join a long-term follow-up study.
详细描述
Background:
- Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapies have had clinical success in a minority of unselected patients across multiple tumor types
- While many questions remain about optimal PD1/PDL1 staining techniques to pre-select responders, less focus is being place on how to optimize responses in a broader cohort of patients
- Emerging preclinical and clinical data supports the hypothesis that a strong immunologic response in the tumor microenvironment induces PDL1 expression on the tumor and is associated with better clinical response to anti-PD1/PDL1 therapies
- Therapeutic cancer vaccines are one strategy to induce an immunologic response to the tumor, thereby enhancing PDL1 expression and optimizing clinical responses across all patients
- Limited clinical data exists about the potential benefit of sequential therapy with a therapeutic cancer vaccine followed by PD1/PDL1 inhibition
- This study will explore the role of PD1 inhibition in medullary thyroid cancer and evaluate the potential differences based on previous vaccine therapy
Objective:
-The primary objective of this trial is to determine whether administering a PD1 inhibitor to patients with medullary thyroid cancer will permit a modest fraction to be able to experience a 50% or greater decline in calcitonin levels or experience a partial/complete response on imaging
Key Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: Participants that had an immune stimulating cancer vaccine
Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks for two years.
Group 1: cancer vaccine
干预措施: Pembrolizumab (Drug)
Cohort 2: Participants that have had no vaccine
Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks for two years.
Group 2: had no previous vaccine
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Clinical Response
时间窗: 2 years
Participants with medullary thyroid cancer were administered a programmed cell death protein 1 (PD1) inhibitor to determine if any experienced a 50% or greater decline in calcitonin levels. A calcitonin response is defined as participants with a ≥50% decline from baseline that is then confirmed on a subsequent calcitonin assessment at least one week later.
Percentage of Participants With a Partial Response and Complete Response by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
时间窗: 2 years
Participants were imaged by CT or MRI and followed for response using the Immune-Related Response Criteria (irRC). Partial Response is a ≥30% decrease in the sum of the largest diameter (SLD) compared with baseline confirmed by a consecutive assessment at least 4 weeks after the first documentation. Complete Response is a 100% disappearance of all lesions, whether measurable or not, and no new lesions, in two consecutive observations not less than 4 weeks from the date first documented.
次要结局
- Percentage Change in (Cluster of Differentiation 4 (CD4), CD8, Tregs, and Natural Killer (NK) Cells at Day 1 and 84 Days in All Participants(Day 1 and 84 days)
- Number of Participants With a Sustained Decline in Carcinoembryonic Antigen (CEA)(every 3 weeks while on treatment and post treatment, up to 2 years)
- Number of Participants With a Sustained Decline in Calcitonin(every 3 weeks while on treatment and post treatment, up to 2 years)
- Progression-free Survival (PFS)(3 weeks for up to 2 years while on treatment than 2 weeks after last treatment)
- Overall Survival at 2 Years(2 years)
- Number of Participants With Grade ≥1 Adverse Events Possibly, Probably, or Definitely Related to Pembrolizumab(Date treatment consent signed to date off study, approximately 25 months and 28 days for cohort 1 and 18 months and 12 days for cohort 2.)
- Number of Participants With Grade ≥1 Adverse Events Unlikely or Unrelated to Pembrolizumab(Date treatment consent signed to date off study, approximately 25 months and 28 days for cohort 1 and 18 months and 12 days for cohort 2.)
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)(Date treatment consent signed to date off study, approximately 25 months and 28 days for cohort 1 and 18 months and 12 days for cohort 2.)
研究者
Ravi A. Madan, M.D.
Principal Investigator
National Cancer Institute (NCI)